Diisopropylethylamine → 5-(3-((1R,2S)-1-(Cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

HRID 1025120노트

반응식

HRID 1025120 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([C:21]4[CH:22]=[C:23]([CH:27]=[CH:28][CH:29]=4)[C:24](O)=[O:25])=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:4][CH:3]=1.CC1C=CC(S(O)(=O)=O)=CC=1.[NH2:41][C@:42]1([C:47]([NH:49][S:50]([CH:53]2[CH2:55][CH2:54]2)(=[O:52])=[O:51])=[O:48])[CH2:44][C@H:43]1[CH:45]=[CH2:46].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CO.CN(C=O)C>[CH:53]1([S:50]([NH:49][C:47]([C@@:42]2([NH:41][C:24]([C:23]3[CH:22]=[C:21]([C:18]4[CH:19]=[CH:20][C:10]5[O:9][C:8]([C:5]6[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=6)=[C:12]([C:13]([NH:14][CH3:15])=[O:16])[C:11]=5[CH:17]=4)[CH:29]=[CH:28][CH:27]=3)=[O:25])[CH2:44][C@H:43]2[CH:45]=[CH2:46])=[O:48])(=[O:52])=[O:51])[CH2:55][CH2:54]1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 592754243-[2-(4-Fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-5-yl]benzoic acidHCID 72163227Cyclopropanecarboxamide, 1-amino-N-(cyclopropylsulfonyl)-2-ethenyl-, (1R,2S)-, 4-methylbenzenesulfonate (1:1)

생성물 1

HCID 592751245-(3-((1R,2S)-1-(Cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide수율 55.4%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6228Dimethylformamide용매

실험 절차

In a 7 mL scintillation vial were combined 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)benzoic acid (30 mg, 0.077 mmol), (1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide 4-methylbenzenesulfonate (30 mg, 0.075 mmol), and HATU (40 mg, 0.10 mmol). DMF (0.4 mL) and DIPEA (0.1 mL, 0.57 mmol) were added, the vial was capped, and the solution was stirred at r.t. for 45 min. The reaction was diluted with MeOH, filtered, purified by prep HPLC, and the collected fractions were concentrated on a speedvac to afford the title compound (25 mg, 54% yield) as a white powder. 1H NMR (500 MHz, CDCl3) δ ppm 8.01 (s, 1 H) 7.97 (s, 1 H) 7.88 (dd, J=8.85, 5.19 Hz, 2 H) 7.80 (d, J=7.63 Hz, 1 H) 7.74 (d, J=7.63 Hz, 1 H) 7.59 (br. s., 1 H) 7.52 (s, 2 H) 7.48 (t, J=7.63 Hz, 1 H) 7.18 (t, J=8.55 Hz, 2 H) 6.00 (d, J=3.97 Hz, 1 H) 5.61-5.73 (m, 1 H) 5.39 (d, J=17.09 Hz, 1 H) 5.20 (d, J=10.99 Hz, 1 H) 3.02 (d, J=4.88 Hz, 3 H) 2.91-2.99 (m, 1 H) 2.34 (q, J=8.44 Hz, 1 H) 2.05-2.09 (m, 1 H) 1.49 (dd, J=9.31, 5.95 Hz, 1 H) 1.41 (dd, J=5.80, 4.58 Hz, 1 H) 1.30-1.35 (m, 1H) 1.22-1.30 (m, 1 H) 1.04-1.12 (m, 1 H) 0.96-1.04 (m, 1 H). LC/MS was performed by using Shimadzu-VP instrument with UV detection at 220 nm and Waters Micromass. LC/MS method: solvent A=10% CH3CN/90% H2O/0.1% TFA, solvent B=90% CH3CN/10% H2O/0.1% TFA, start % B=0, final % B=100, gradient time=2 min, stop time=3 min, flow rate=4 ml/min, column: Sunfire C18 5 μm 4.6×50 mm; HPLC Rt=1.73 min, (ES+) m/z (MH+)=602. Analytical HPLC were performed using a Shimadzu-VP instrument with UV detection at 220 nm and 254 nm. Analytical HPLC method: solvent A=5% CH3OH/95% H2O/10 mM NH4HCO3, solvent B=95% CH3OH/5% H2O/10 mM NH4HCO3, start % B=10, final % B=100, gradient time=15 min, stop time=18 min, flow rate=1 ml/min. Column: Phenomenex Gemini C18, 4.6 mm, 3 μm, Rt=16.26 min, purity=100%; column: Waters Xbridge Phenyl 4.6×150 mm, 3.5 μm, Rt=15.28 min, purity=100%.

후처리

  1. customthe vial was capped
  2. filtrationfiltered
  3. custompurified by prep HPLC
  4. concentrationthe collected fractions were concentrated on a speedvac

출처 및 근거

ORD 기록
ord-a39a64f7b5444c54a0e93360b2c271b3
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08722688B2

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